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At least 433 records · Page 24Linked to original sources
PubMed1999

Adenosine inhibits the renal plasma-membrane (Ca2+ + Mg2+)-ATPase through a pathway sensitive to cholera toxin and sphingosine.

Adenosine, a potent autacoid produced and released in kidneys, affects nearly all aspects of renal function, and an increase in cytosolic calcium has been implicated in adenosine effects. The aim of this work was to investigate whether adenosine modifies the calcium pump present in basolateral membranes of kidney proximal tubule cells. Adenosine exerts a biphasic influence on (Ca2+ + Mg2+)-ATPase activity. Inhibition occurs up to 0.1 microM and then gradually disappears as the adenosine concentration increases to 100 microM, an effect mimicked by the adenosine analog N6-cyclohexyladenosine, which preferentially binds to A1-type receptors. In contrast, the A2 receptor agonist 5', N-ethylcarboxamideadenosine is ineffective. The A1 receptor antagonist 8-cyclopentyl-1,3-dimethylxanthine blocks the inhibitory effect of 0.1 microM adenosine and stimulates (Ca2+ + Mg2+)-ATPase activity in the presence of 1 mM adenosine, a concentration high enough to occupy the low-affinity A2 receptors. Inhibition by adenosine increases as medium ATP is lowered to micromolar concentrations, is maintained in the presence of pertussis toxin, and is completely abolished with 0.1 microM cholera toxin or 1 microM sphingosine. The inhibitory effect of adenosine can be reproduced by guanosine 5'-[gamma-thio]triphosphate, inositol 1,4, 5-trisphosphate or the diacylglycerol analog 12-O-tetradecanoylphorbol 13-acetate. In conjunction with the selectivity for its analogs and for its receptor agonist, the concentration profile of adenosine effects indicates that both inhibitory (A1) and stimulatory (A2) receptors are involved. The results obtained with the toxins indicate that a pathway that is modulated by G-proteins, involves a phospholipase C and a protein kinase C, and is affected by local variations in adenosine concentrations participates in the regulation of the (Ca2+ + Mg2+)-ATPase resident in basolateral membranes of kidney proximal tubules.

Adenosine↗
PubMed1999

Homocysteine decreases endothelin-1 production by cultured human endothelial cells.

Hyperhomocysteinemia is believed to be responsible for the development of vascular disease via several mechanisms, including the impairment of endothelial-cell functionality. In-vitro studies have demonstrated that homocysteine decreases the production or bioavailability of vasodilator autacoids, such as prostacyclin and NO. Here, we show that the treatment of human endothelial cells with noncytotoxic homocysteine concentrations leads to a dose-dependent decrease in both the secretion of the vasoconstrictor agent endothelin-1 (ET-1) and the level of its mRNA. Homocysteine had an inhibitory effect at pathophysiological (0.1 and 0.5 mmol.L(-1)) and pharmacological noncytotoxic (1.0 and 2.0 mmol.L(-1)) concentrations. Mean percentage variation from control for ET-1 production was -36. 2 +/- 18.9% for 0.5 mmol.L(-1) homocysteine and -41.5 +/- 26.8% for 1.0 mmol.L(-1) homocysteine, after incubation for 8 h. Mean percentage variation from control for steady-state mRNA was -17.3 +/- 7.1% for 0.5 mmol.L(-1) homocysteine and -46.0 +/- 10.1 for 1.0 mmol.L(-1) homocysteine, after an incubation time of 2 h. ET-1 production was also reduced by incubation with various other thiol compounds containing free thiol groups, but not by incubation with thiol compounds with no free thiol group. Co-incubation of cells with homocysteine and the sulfhydryl inhibitor N-ethylmaleimide prevented the effect of homocysteine on ET-1 production, confirming a sulfhydryl-dependent mechanism. Based on the reciprocal feedback mechanism controlling the synthesis of vasoactive mediators, these preliminary data suggest a mechanism by which homocysteine may selectively impair endothelium-dependent vasodilation by primary inhibition of ET-1 production.

Arteriosclerosis↗
PubMed2000

Effect of age on the responses of rat bladder detrusor strips to adenosine triphosphate.

OBJECTIVE: To assess age-related changes in bladder function using the contractile responses to ATP of detrusor strips from rats of various ages. Materials and methods Urinary bladders were obtained from male Wistar rats aged 9 weeks (young), 24 weeks (adult) and 24 months (aged). Contractions of urinary bladder muscle strips to ATP were measured isometrically. The size of the initial phasic response and the secondary contractile response that developed after washing out ATP (postwashout contraction) were measured. The magnitudes of the ATP-induced phasic and postwashout contraction were compared among the age groups. During the contractions, prostanoid concentrations in the organ-bath medium were measured using an enzyme immunoassay. RESULTS: The ATP-induced postwashout contraction did not occur after stimulation with KCl or acetylcholine, but was induced by alpha,beta-methylene ATP. Both the phasic and postwashout contractions were concentration-dependent. Although the phasic contraction did not change progressively with age, the magnitude and duration of the postwashout contraction increased substantially with age. Nicardipine (a calcium antagonist) slightly inhibited both contractions. Suramin (a nonselective P2-receptor antagonist) did not significantly inhibit the phasic contraction, but reduced the postwashout contraction. PPADS (a selective P2X receptor antagonist) did not inhibit either contraction. Indomethacin (a prostaglandin synthesis inhibitor) had no effect on the phasic contraction but almost completely blocked the postwashout contraction when added before ATP stimulation, but was less effective when added after ATP. The prostaglandin E2 concentration in the organ bath increased during the postwashout contraction. CONCLUSIONS: These findings suggest that the ATP-induced postwashout contraction is not directly mediated by P2x purinoceptors, but results from the synthesis of prostaglandins, especially E2, which is a sensory autacoid. The age-linked increase in postwashout contraction may be involved in the changes in sensory and voiding mechanisms seen in the aged urinary bladder.

Acetylcholine↗
PubMed1995

myc-immortalized microglial cells express a functional platelet-activating factor receptor.

The autacoid platelet-activating factor (PAF) takes part in a complex network of interactions regarding the cellular components of nervous tissues. Efforts aimed at characterizing the effects of PAF in the brain have been recently focalized on neurons because PAF exerts pleiotropic effects on these cells. Less attention has instead been paid to the glial component of the brain. We have used microglial cell lines immortalized from 13-day-old mouse embryo brains by a myc-transducing retrovirus. When exposed to physiological doses of PAF, immortalized microglial cells showed increases in intracellular free calcium concentrations due to release of calcium from internal stores, as well as to extracellular calcium influxes. These profiles of reactivity were independent from the immortalizing process, being observable in primary microglial cultures and in immortalized clones showing different proliferative rates. PAF was also able to induce transient expression of the c-fos protooncogene in serum-starved cultures and induced a strong chemotactic response in microglial cells. In contrast with control macrophage cultures, PAF did not promote prostaglandin or leukotriene synthesis in immortalized cells. This was most likely due to the low amount of total arachidonic acid found in immortal microglia, with respect to that observed in freshly isolated cells. Our data suggest that several of the effects observed after PAF stimulation might be independent from PAF-induced arachidonic acid metabolism. The availability of an in vitro microglial model might now help in studying the proinflammatory effects of PAF, both direct or microglia mediated, in the neural environment.

Animals↗
PubMed1996

Mast cell activation causes delayed neurodegeneration in mixed hippocampal cultures via the nitric oxide pathway.

Mast cells are pleiotropic bone marrow-derived cells found in mucosal and connective tissues and in close apposition to neurons, where they play important roles in tissue inflammation and in neuroimmune interactions. Connective tissue mast cells, with which intracranial mast cells share many characteristics, contain cytokines that can cause inflammation. Here, we report that myelin basic protein, a major suspected immunogen in multiple sclerosis, as well as an antigenic stimulus, provokes mast cells to trigger a delayed cytotoxicity for neurons in mixed neuron-gila cultures from hippocampus. Neurotoxicity required a prolonged period (12 h) of mast cell incubation, and appeared to depend largely on elaboration of the free radical nitric oxide by astrocytes. Activation of astrocytes was mediated, in part, by mast cell-secreted tumor necrosis factor-alpha. Myelin basic protein and 17 beta-estradiol had a synergistic action on the induction of mast cell-associated neuronal injury. The cognate mast cell line RBL-2H3, when subjected to an antigenic stimulus, released tumor necrosis factor-alpha which, together with exogenous interleukin-1 beta (or interferon-gamma), induced astroglia to produce neurotoxic quantities of nitric oxide. A small but significant proportion of mast cell-derived neurotoxicity under the above conditions occurred independently of glial nitric oxide synthase induction. Further, palmitoylethanolamide, which has been reported to reduce mast cell activation by a local autacoid mechanism, decreased neuron loss resulting from mast cell stimulation in the mixed cultures but not that caused by direct cytokine induction of astrocytic nitric oxide synthase. These results support the notion that brain mast cells could participate in the pathophysiology of chronic neurodegenerative and inflammatory diseases of the nervous system, and suggest that down-modulation of mast cell activation in such conditions could be of therapeutic benefit.

Amides↗
PubMed1998

Localization of the prostacyclin receptor in human kidney.

BACKGROUND: Prostacyclin is an important mediator of renal hemodynamics. Furthermore, recent studies argue for a role of this arachidonic acid metabolite in the regulation of salt and water handling in the distal nephron. To gain insight into the network of prostacyclin signal transduction, we analyzed the intrarenal distribution of the prostacyclin receptor (IP receptor) in adult human kidney. METHODS: Specific polyclonal antibodies against a synthetic peptide of the human IP receptor were generated. By means of immunohistology the localization of IP receptor protein was studied. The mRNA expression for IP receptor was analyzed by in situ hybridization using specific cRNA probes. RESULTS: In human kidney sections both IP receptor-immunoreactive protein and mRNA were expressed in smooth muscle cells and endothelial cells. Expression of the IP receptor was observed in glomerular cells, namely mesangial cells, endothelial cells, and podocytes. Both mRNA and protein expression for IP receptor was observable in Tamm-Horsfall-negative distal tubules and collecting ducts. CONCLUSIONS: The vascular expression of the IP receptor is consistent with the known vasodilatory effect of prostacyclin in vascular beds. Glomerular expression argues for a role of this autacoid in the regulation of glomerular hemodynamics. The tubular distribution might point towards the involvement of prostacyclin in renal salt and water handling.

Endothelium, Vascular↗
PubMed1998

Regulation of renal function by prostaglandin E receptors.

Prostaglandin E2 is the major cyclooxygenase product of arachidonic acid metabolism produced along the nephron. This autacoid interacts with four distinct, G-protein-coupled E-prostanoid receptors designated EP1-EP4. The intrarenal distribution of each receptor has been mapped and the consequences of receptor activation examined. EP3 receptor mRNA is expressed highly in the medullary thick ascending limb (mTAL) and collecting duct (CD). EP3 receptor activation inhibits cAMP generation via Gi, thus inhibiting vasopressin-stimulated water reabsorption in the CD. EP3 receptor activation also may contribute to PGE2-mediated inhibition of NaCl absorption in the mTAL. The EP1 receptor is coupled to increased cell [Ca2+]. EP1 mRNA expression is restricted to the CD, and receptor activation inhibits Na+ absorption. PGE2 also increases cAMP generation in the cortical thick ascending limb and CD; this may be due to EP4 receptor activation. EP4 mRNA is readily detected in the CD with little detectable EP2 expression. The EP4 receptor appears to be expressed both on luminal and basolateral membranes. EP4 receptor activation also may contribute to the regulation of renin release by the juxtaglomerular apparatus. The consequences of renal EP-receptor activation for salt and water balance may be determined by the relative renal expression of each of these receptors.

Animals↗
PubMed2003

[Functional duality of kinin receptors in pathophysiology].

Kinins are autacoid peptides and central neuromediators involved in cardiovascular regulation, inflammation and pain. Their effects are mediated by two transmembrane G-protein-coupled receptors denoted as B1 and B2. While the B2 receptor is constitutive, the B1 receptor is inducible and up-regulated in the presence of cytokines, endotoxins or during tissue injury. The B2 receptor is believed to play an important role in the beneficial effects of angiotensin-1 converting enzyme inhibitors used in the treatment of cardiovascular diseases, yet it is involved in the acute phase of inflammation and of somatic and visceral pain. Conversely, the B1 receptor participates in the chronic phase of these responses and is likely to play a strategic role in diseases with a strong immune component such as rheumatoid arthritis, multiple sclerosis, septic shock and diabetes. A dual function for the B1 receptor is also reported in some pathologies in which it can exert either a protective (multiple sclerosis and septic shock) or harmful (pain and inflammation) effect. Therefore, the use of antagonists for these receptors as clinical therapeutic agents requires a rigorous evaluation of the potential side effects.

Arthritis, Rheumatoid↗
PubMed2002

Effects of TNFalpha-antagonists on nitric oxide production in human cartilage.

OBJECTIVE: Nitric oxide (NO) produced by cartilage and synovial membrane is implicated in the pathogenesis of osteoarthritis (OA) and rheumatoid arthritis (RA). In inflamed joints NO is synthesized in response to proinflammatory cytokines and it is involved in the joint destruction. The aim of the present study was to investigate the effects of TNFalpha-antagonists infliximab and etanercept on NO production in human cartilage. DESIGN: Cartilage specimen obtained from OA patients undergoing knee replacement surgery were studied for iNOS expression and NO production in organ culture to allow intact chondrocyte-matrix interactions. TNFalpha and soluble TNFalpha receptor release was measured by ELISA. RESULTS: Osteoarthritic cartilage produced NO spontaneously and its production was enhanced by proinflammatory cytokines TNFalpha (tumor necrosis factor alpha), IL-1beta (interleukin-1beta), IL-17 (interleukin-17) and by bacterial lipopolysaccharide (LPS). TNFalpha-antagonists infliximab and etanercept inhibited TNFalpha-induced NO production in a dose dependent manner but they had no effect on IL-1beta-, IL-17- and LPS-stimulated NO synthesis. TNFalpha and soluble TNFalpha receptors (sTNFRI and sTNFRII) were produced by human osteoarthritic cartilage. A neutralizing antibody against soluble TNFRI enhanced spontaneous NO production whereas an antibody against soluble TNFRII had no effect. CONCLUSIONS: TNFalpha-antagonists infliximab and etanercept suppressed TNFalpha-induced NO production. This effect was not seen on IL-1-, IL-17- or LPS-induced NO production suggesting that TNFalpha is not an autacoid mediator in these processes. The studies with neutralizing antibodies against soluble TNFRI suggest that endogenous cartilage-derived TNFalpha-antagonists modulate NO production in osteoarthritic cartilage.

Aged↗
PubMed2002

[Neurogenic inflammation. I. Basic mechanisms, physiology and pharmacology].

Activation of sensory unmyelinated neurons by noxious stimuli evokes the release of neuropeptides, such as substance P and calcitonin gene-related peptide (CGRP) from peripheral nerve endings. These neuropeptides and subsequently released mediators cause a local oedema, hyperaemia and an erythema which extends beyond the site of stimulation (so-called flare response). Since these inflammatory signs depend on the function and integrity of peripheral sensory nervous systems, the response has been termed neurogenic inflammation. Due to the fact that nearly all tissues in mammals including humans are innervated by afferent sensory neurons, this neurogenic inflammation can occur ubiquitously throughout the body. Albeit first evidence showing that sensory neurons contribute to the inflammatory signs, described as antidromic vasodilatation, axon reflex, triple response, neurogenic inflammation, elicited at the level of tissue that they innervate was first obtained more than one hundred years ago, it was in the last two decades that inflammation caused by the release of neuropeptides from afferent nerve endings was recognised as a physiologically and pathologically relevant process. A large number of exogenous and endogenous substances and autacoids may stimulate or sensitise sensory nerve endings, thus simultaneously producing pain and nociceptive responses, as well as neurogenic inflammation. On the basis of recent research a variety of pharmacological substances and antagonists of putative mediators have been identified to modulate or suppress neurogenic inflammation, thus providing a rationale for therapeutical strategies for various diseases in which neurogenic inflammation is suggested to be involved. Among them, capsaicin and other newly developed agonists and antagonists at the vanilloid receptor have attracted particular attention, since they were found to be capable of desensitizing nociceptive nerve structures and thus of preventing development of neurogenic inflammation or even of abolishing an ongoing inflammatory process.

Animals↗
PubMed2003

Myorelaxant effects of the essential oil of Croton nepetaefolius on the contractile activity of the guinea-pig tracheal smooth muscle.

The effects of the essential oil of Croton nepetaefolius (EOCN) on isolated guinea-pig trachea were investigated. EOCN decreased the preparation's basal tone (EC (50) = 4.3 microg/mL) with a maximal effect similar to that of aminophylline. EOCN fully relaxed preparations pre-contracted with 60 mM K+ (IC (50) = 113.0 microg/mL). EOCN did not alter the E (m) of smooth muscle cells in 5 and 80 mM K+. EOCN, at 300 and 600 microg/mL, reduced the contraction induced by ovalbumin (10 microg/mL) from 227.2 to 82.5 and 35.5 % of the 60 mM K+-induced contraction, respectively. EOCN blocked the submaximal contractions induced by histamine, carbachol and 60 mM K+ with a similar potency (IC (50) values = 123.9, 102.5 and 128.8 microg/mL, respectively). In conclusion, EOCN exerts respiratory smooth muscle antispasmodic activity by a mechanism that is probably myogenic and not specific for neurotransmitters and autacoids.

Animals↗
PubMed2003

Antispasmodic effect of the essential oil of Plectranthus barbatus and some major constituents on the guinea-pig ileum.

The effects of the Plectranthus barbatus essential oil (PBEO) at concentrations ranging form 1 to 300 microg/mL and some major constituents, i. e., alpha-pinene, myrcene and caryophyllene in the ratio and amount found in the oil, were studied on the contractility of the guinea-pig ileum. PBEO decreased the basal tonus of the ileum with a maximal response (R (max); % of K (+)-contraction) of 62.7 +/- 3.8 % compared with 36.6 +/- 4.5 % inhibition achieved with alpha-pinene and 68 +/- 2.6 % with papaverine. The other constituents had only a slight effect. PBEO also blocked the phasic contractions evoked by acetylcholine with an R (max) of 85 +/- 3.6 % compared with 54.4 +/- 3.5 % inhibition induced by alpha-pinene and 12.4 +/- 5.6 % with caryophyllene. The contractions induced by histamine or barium chloride were also decreased in amplitude by PBEO with an R (max) of 94.3 +/- 5.7 % and 100 %, respectively. In addition, PBEO relaxed tissues pre-contracted with 60 mM K (+) with an R (max) of 89.7 +/- 2.7 % compared with 55.4 +/- 4.6 % relaxation induced by alpha-pinene. The other major constituents studied had no significant effect. Furthermore, at the higher concentration used, i. e., 300 microg/mL, PBEO decreased the maximal response of calcium chloride (10 ( - 7) to 10 ( - 3) M) induced contraction in depolarized tissues by 29.1 +/- 9.53 % (p < 0.05). In addition, the component of the contraction elicited by a single dose of carbachol (CCh; 100 microM) added on nifedipine (10 microM) treated tissues or at very low extracellular calcium concentration were blocked by PBEO (300 microg/mL) in 85.7 +/- 7.8 % (p < 0.05; n = 5) and 81.2 +/- 6.4 % (p < 0.05; n = 4), respectively. These data show that PBEO has intestinal relaxant and antispasmodic activity and suggest that this effect is not related to antagonism in extracellular receptors for neurotransmitters or autacoids and it seems to occur downstream of calcium entry or release from internal stores. The main active principle for its relaxant and spasmolytic activity seems to be alpha-pinene.

Animals↗
PubMed1982

Influence of insulin and glucagon on the production of glomerulopressin by isolated rat liver.

Isolated rats livers were perfused with Krebs-Ringer-Bicarbonate (KRB) and different doses of insulin or glucagon and with insulin plus glucagon. The isolated liver of fasted rats and of rats treated with streptozotocin were perfused with (KRB). The glomerulopressin activity of the ultrafiltrate of the liver perfusates were assayed in the tonic tension contraction (TTC) of isolated stomach fundus from rats. As glomerulopressin is known to be a glucuronide, it was inactivated with beta-glucuronidase to confirm that the effect on the stomach fundus was due to the glomerulopressin and not to an autacoid. It was observed that glucagon increased the glomerulopressin activity of the perfusate and that this activity was independent of the dose of glucagon used. Insulin produced a decrease in the glomerulopressin activity of the perfusate, there being a log-dose relationship between insulin and glomerulopressin. There is a dose of insulin (1,5 X 10(-5) U/min/kg) that potentiates the response to glucagon. Fasting and treatment with streptozotocin induced an increase in the glomerulopressin activity of the perfusate. These results suggest that glomerulopressin production is influenced by glucagon and insulin, and that there is a specific ratio between these hormones that is very effective in the production of glomerulopressin.

Animals↗
PubMed1990

Effects of indomethacin, during pregnancy in the rat, on responses to noradrenaline and angiotensin II in vivo, and responses to phenylephrine in vitro.

Pressor responses to both angiotensin II (Ang II) and noradrenaline (NA) were reduced in 20-day-pregnant rats compared with those in non-pregnant animals, regardless of whether the results were expressed in terms of the dose per kilogram of body weight or per millilitre of estimated plasma volume. Inhibition of prostaglandin production with indomethacin (10 mg kg-1, i.v.) was not accompanied by any significant effect on responses to Ang II in either non-pregnant or 20-day-pregnant animals. However, it attenuated the effects of NA in 20-day-pregnant rats. Indomethacin (10(-5) or 3 x 10(-5) M) did not potentiate in vitro vasoconstrictor responses to phenylephrine of endothelium-intact or -denuded thoracic aortic rings from non-pregnant or 20-day-pregnant rats. These results suggest that subsensitivity to Ang II or NA during pregnancy in the rat is not due to dilution of the dose of these autacoids resulting from increased plasma volume, nor to an increased output of vasodilator prostaglandins.

Angiotensin II↗
PubMed1991

Regulation of fetal vascular tone in the human placenta.

Using an in vitro placental lobule perfusion technique, the human fetal placental vasculature has been found to respond vigorously with high sensitivity to various vasoconstrictor substances, including angiotensin II, endothelins 1 and 3, prostaglandins F2 alpha, E2 and D2 and the thromboxane A2 agonist U46619. Thromboxane A2 receptors mediating vasoconstriction have been characterized in fetal placental vessels and appear to be identical to those on human platelets and pulmonary blood vessels. Although the isolated fetal placental vessels are largely unresponsive to exogenous vasodilatory stimuli, when preconstricted they respond by vasodilatation to several vasodilator substances, including arachidonate, prostacyclin, prostaglandin E1, theophylline and nitroglycerine. The resistance offered to flow in vitro by the villous vasculature is therefore low, as it is in vivo. Both intrinsic and extrinsic mechanisms probably operate to cause relaxation of the vascular smooth muscle with the vasodilatory effects of locally released autacoids dominating the effects of those having vasoconstrictor actions.

Female↗
PubMed1995

Regulation of human placental fetal vessel tone: role of nitric oxide.

Factors affecting fetal vessel resistance have been studied in vitro in bilaterally perfused lobules of human placentae. Potent and efficacious constrictors in this preparation (in order of potency) include endothelin-1 > the thromboxane mimetic U46619 > endothelin-3 > prostaglandin F2 alpha. Inhibitors of eicosanoid synthesis did not affect fetal vessel basal perfusion pressure, nor did they potentiate the effects of the vasoconstrictor U46619. In contrast, the nitric oxide inhibitors N omega-nitro-L-arginine (NOLA), haemoglobin and methylene blue all increased fetal vessel basal perfusion pressure and also increased U46619-induced constriction. Similarly, NOLA markedly potentiated the constrictor effects of endothelin-1, angiotensin II, 5-hydroxytryptamine and bradykinin. These studies therefore provide evidence that NO is important in the maintenance of low basal fetal vessel impedance and also reduces the effects of a number of vasoconstrictor autacoids. Nitric oxide synthase (NOS) activity of human placental homogenates has been measured and shown to be mainly calcium-dependent. Human placental NOS activity was not affected by labour state but was reduced in pre-eclampsia. No evidence was found that in pre-eclampsia raised concentrations of the endogenous NOS inhibitor asymmetric dimethylarginine were responsible for the reduced placental NOS activity. Hence, these studies provide evidence that NO is an important endogenous dilator of the fetal vessels of the human placenta and that reduced NOS activity could contribute to the pathogenesis and/or effects of pre-eclampsia.

Enzyme Inhibitors↗
PubMed1989

Deficiencies of polyunsaturated fatty acids and replacement by nonessential fatty acids in plasma lipids in multiple sclerosis.

Fatty acid compositions of plasma phospholipids, cholesteryl esters, triacylglycerols, and nonesterified fatty acids of 14 clinically proven and graded cases of multiple sclerosis were determined by capillary gas chromatography and compared with the values obtained for 100 normal, healthy subjects. In phospholipids, linoleic acid (18:2 omega 6; 18 carbon atoms, 2 double bonds, 6 carbon atoms beyond last double bond) was normal and 18:3 omega 6 was increased, but all subsequent omega 6 acids were subnormal (P less than 0.001), indicating impairment of chain elongation. All omega 3 acids were subnormal. The paucity of polyunsaturated fatty acids was compensated mass-wise by an increase in saturated acids. Disproportionate increases in short-chain, saturated, and monounsaturated acids, decreases in long-chain homologs, and increases of branched and odd-chain acids were observed. Loss of polyunsaturated fatty acids and replacement by nonessential acids lowered mean chain length and raised mean melting point significantly, suggesting that lowered membrane fluidity was only partially compensated by endogenous synthesis of lower-melting, nonessential acids. This phenomenon was not observed in cholesteryl esters or triacylglycerols. Nonesterified fatty acids showed significant changes in pattern of possible autacoid precursors. The abnormal profile of fatty acids in multiple sclerosis has features in common with profiles of other syndromes involving viral infections.

Adult↗
PubMed1991

Unusual isomeric polyunsaturated fatty acids in liver phospholipids of rats fed hydrogenated oil.

Linoleic acid (18:2 omega 6) and linolenic acid (18:3 omega 3) are precursors of two series of essential fatty acids (EFA) formed by alternate desaturations and elongations. In EFA deficiency (EFAD), oleic acid (18:1 omega 9) and palmitoleic acid (16:1 omega 7) undergo the same reactions to form polyunsaturated fatty acids (PUFA) of other structures. Partially hydrogenated soybean oil (PHSO) contains isomeric 18:1 acids that can be converted to unusual isomers of 18:2 by liver microsomes. To test whether 18:2, 20:3, and 20:4 of unusual structure occur in phospholipids as a consequence of EFAD or ingestion of PHSO, rats were fed corn oil, an EFA-deficient diet, or PHSO to provide isomeric 18:1 acids. At 2.5 months the phospholipids were isolated from livers and converted to methyl esters, and the 18:2, 20:2, 20:3, and 20:4 fractions were isolated. The 18:2 and 20:2 fractions were ozonized, and, by using a computer solution of simultaneous equations, the structures and proportions of each isomer were calculated. The 20:3 and 20:4 fractions were analyzed by ozonolysis and capillary gas chromatography. When corn oil was fed, the major isomer in each group was 9,12-18:2, 11,14-20:2, 8,11,14-20:3, and 5,8,11,14-20:4. Patterns in EFAD- and PHSO-fed groups were more diverse, with large proportions of unusual isomers. Feeding EFA-deficient diet and PHSO induced measurable amounts of unusual PUFA at each step of the cascade, and these PUFA may compete in metabolism of normal PUFA and are substrates for oxidative formation of autacoids of unknown structures and function.

Animals↗